Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis

Autores
Sánchez Valdéz, Fernando Javier; Perez Brandan, Cecilia Maria; Zago, María Paola; Labriola, Carlos Alberto; Ferreira, Arturo; Basombrio, Miguel Angel Manuel
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Trypanosoma cruzi calreticulin (TcCRT) can hijack complement C1, mannan-binding lectin and ficolins from serum thus inhibiting the classical and lectin complement pathway activation respectively. To understand the in vivo biological functions of TcCRT in T. cruzi we generated a clonal cell line lacking one TcCRT allele (TcCRT+/-) and another clone overexpressing it (TcCRT+). Both clones were derived from the TCC T. cruzi strain. As expected, TcCRT+/- epimastigotes showed impairment on TcCRT synthesis, whereas TcCRT+ ones showed increased protein levels. In correlation to this, monoallelic mutant parasites were significantly susceptible to killing by the complement machinery. On the contrary, TcCRT+ parasites showed higher levels of resistance to killing mediate by the classical and lectin but not the alternative pathway. The involvement of surface TcCRT in depleting C1 was demonstrated through restoration of serum killing activity by addition of exogenous C1. In axenic cultures, a reduced propagation rate of TcCRT+/- parasites was observed. Moreover, TcCRT+/- parasites presented a reduced rate of differentiation in in vitro assays. As shown by down- or upregulation of TcCRT expression this gene seems to play a major role in providing T. cruzi with the ability to resist complement system.
Fil: Sánchez Valdéz, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina
Fil: Perez Brandan, Cecilia Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina
Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina
Fil: Labriola, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ferreira, Arturo. Universidad de Chile; Chile
Fil: Basombrio, Miguel Angel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina
Materia
Calreticulin
Complement
C1
Knock-Out
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/19657
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/19657
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesisSánchez Valdéz, Fernando JavierPerez Brandan, Cecilia MariaZago, María PaolaLabriola, Carlos AlbertoFerreira, ArturoBasombrio, Miguel Angel ManuelCalreticulinComplementC1Knock-Outhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trypanosoma cruzi calreticulin (TcCRT) can hijack complement C1, mannan-binding lectin and ficolins from serum thus inhibiting the classical and lectin complement pathway activation respectively. To understand the in vivo biological functions of TcCRT in T. cruzi we generated a clonal cell line lacking one TcCRT allele (TcCRT+/-) and another clone overexpressing it (TcCRT+). Both clones were derived from the TCC T. cruzi strain. As expected, TcCRT+/- epimastigotes showed impairment on TcCRT synthesis, whereas TcCRT+ ones showed increased protein levels. In correlation to this, monoallelic mutant parasites were significantly susceptible to killing by the complement machinery. On the contrary, TcCRT+ parasites showed higher levels of resistance to killing mediate by the classical and lectin but not the alternative pathway. The involvement of surface TcCRT in depleting C1 was demonstrated through restoration of serum killing activity by addition of exogenous C1. In axenic cultures, a reduced propagation rate of TcCRT+/- parasites was observed. Moreover, TcCRT+/- parasites presented a reduced rate of differentiation in in vitro assays. As shown by down- or upregulation of TcCRT expression this gene seems to play a major role in providing T. cruzi with the ability to resist complement system.Fil: Sánchez Valdéz, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaFil: Perez Brandan, Cecilia Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaFil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaFil: Labriola, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ferreira, Arturo. Universidad de Chile; ChileFil: Basombrio, Miguel Angel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaElsevier2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/19657Sánchez Valdéz, Fernando Javier; Perez Brandan, Cecilia Maria; Zago, María Paola; Labriola, Carlos Alberto; Ferreira, Arturo; et al.; Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis; Elsevier; Molecular Immunology; 53; 3; 3-2013; 198-2050161-58901872-9142CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0161589012003604info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molimm.2012.08.001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:53:53Zoai:ri.conicet.gov.ar:11336/19657instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:53:53.549CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis
title Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis
spellingShingle Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis
Sánchez Valdéz, Fernando Javier
Calreticulin
Complement
C1
Knock-Out
title_short Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis
title_full Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis
title_fullStr Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis
title_full_unstemmed Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis
title_sort Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis
dc.creator.none.fl_str_mv Sánchez Valdéz, Fernando Javier
Perez Brandan, Cecilia Maria
Zago, María Paola
Labriola, Carlos Alberto
Ferreira, Arturo
Basombrio, Miguel Angel Manuel
author Sánchez Valdéz, Fernando Javier
author_facet Sánchez Valdéz, Fernando Javier
Perez Brandan, Cecilia Maria
Zago, María Paola
Labriola, Carlos Alberto
Ferreira, Arturo
Basombrio, Miguel Angel Manuel
author_role author
author2 Perez Brandan, Cecilia Maria
Zago, María Paola
Labriola, Carlos Alberto
Ferreira, Arturo
Basombrio, Miguel Angel Manuel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Calreticulin
Complement
C1
Knock-Out
topic Calreticulin
Complement
C1
Knock-Out
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trypanosoma cruzi calreticulin (TcCRT) can hijack complement C1, mannan-binding lectin and ficolins from serum thus inhibiting the classical and lectin complement pathway activation respectively. To understand the in vivo biological functions of TcCRT in T. cruzi we generated a clonal cell line lacking one TcCRT allele (TcCRT+/-) and another clone overexpressing it (TcCRT+). Both clones were derived from the TCC T. cruzi strain. As expected, TcCRT+/- epimastigotes showed impairment on TcCRT synthesis, whereas TcCRT+ ones showed increased protein levels. In correlation to this, monoallelic mutant parasites were significantly susceptible to killing by the complement machinery. On the contrary, TcCRT+ parasites showed higher levels of resistance to killing mediate by the classical and lectin but not the alternative pathway. The involvement of surface TcCRT in depleting C1 was demonstrated through restoration of serum killing activity by addition of exogenous C1. In axenic cultures, a reduced propagation rate of TcCRT+/- parasites was observed. Moreover, TcCRT+/- parasites presented a reduced rate of differentiation in in vitro assays. As shown by down- or upregulation of TcCRT expression this gene seems to play a major role in providing T. cruzi with the ability to resist complement system.
Fil: Sánchez Valdéz, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina
Fil: Perez Brandan, Cecilia Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina
Fil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina
Fil: Labriola, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ferreira, Arturo. Universidad de Chile; Chile
Fil: Basombrio, Miguel Angel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina
description Trypanosoma cruzi calreticulin (TcCRT) can hijack complement C1, mannan-binding lectin and ficolins from serum thus inhibiting the classical and lectin complement pathway activation respectively. To understand the in vivo biological functions of TcCRT in T. cruzi we generated a clonal cell line lacking one TcCRT allele (TcCRT+/-) and another clone overexpressing it (TcCRT+). Both clones were derived from the TCC T. cruzi strain. As expected, TcCRT+/- epimastigotes showed impairment on TcCRT synthesis, whereas TcCRT+ ones showed increased protein levels. In correlation to this, monoallelic mutant parasites were significantly susceptible to killing by the complement machinery. On the contrary, TcCRT+ parasites showed higher levels of resistance to killing mediate by the classical and lectin but not the alternative pathway. The involvement of surface TcCRT in depleting C1 was demonstrated through restoration of serum killing activity by addition of exogenous C1. In axenic cultures, a reduced propagation rate of TcCRT+/- parasites was observed. Moreover, TcCRT+/- parasites presented a reduced rate of differentiation in in vitro assays. As shown by down- or upregulation of TcCRT expression this gene seems to play a major role in providing T. cruzi with the ability to resist complement system.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/19657
Sánchez Valdéz, Fernando Javier; Perez Brandan, Cecilia Maria; Zago, María Paola; Labriola, Carlos Alberto; Ferreira, Arturo; et al.; Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis; Elsevier; Molecular Immunology; 53; 3; 3-2013; 198-205
0161-5890
1872-9142
CONICET Digital
CONICET
url http://hdl.handle.net/11336/19657
identifier_str_mv Sánchez Valdéz, Fernando Javier; Perez Brandan, Cecilia Maria; Zago, María Paola; Labriola, Carlos Alberto; Ferreira, Arturo; et al.; Trypanosoma cruzi carrying a monoallelic deletion of the calreticulin (TcCRT) gene are susceptible to complement mediated killing and defective in their metacyclogenesis; Elsevier; Molecular Immunology; 53; 3; 3-2013; 198-205
0161-5890
1872-9142
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0161589012003604
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molimm.2012.08.001
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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